Cagrilintide

This Phase 2 dose-finding trial randomized 706 adults with body mass index ≥30 (or ≥27 with weight-related comorbidities, without diabetes) across 57 sites in ten countries to once-weekly subcutaneous cagrilintide (0.3, 0.6, 1.2, 2.4, or 4.5 mg), liraglutide 3.0 mg daily, or placebo, over a 26-week treatment period that included up to 6 weeks of dose escalation. At week 26, mean percentage body-weight change was -10.8% at the 4.5 mg cagrilintide dose versus -3.0% with placebo and -9.0% with liraglutide 3.0 mg. Approximately 31% of participants in the 4.5 mg cagrilintide arm achieved ≥15% weight reduction versus 5.2% in placebo. The compound was generally well tolerated; the most common adverse events were gastrointestinal (nausea, decreased appetite) and consistent with the amylin receptor agonist mechanism.

A 26-week study tested five different weekly doses of cagrilintide against placebo and against a daily GLP-1 comparator in adults with overweight or obesity. The highest cagrilintide dose (4.5 mg weekly) produced an average body-weight reduction of about 10.8%, compared with about 3% on placebo. About one in three people on the top dose lost at least 15% of their starting weight. Side effects were mostly stomach-related and matched what would be expected from this class of compound.

This Phase 2 trial evaluated the combination of cagrilintide 2.4 mg plus semaglutide 2.4 mg ("CagriSema") once weekly versus semaglutide 2.4 mg alone and cagrilintide 2.4 mg alone in adults with type 2 diabetes inadequately controlled on metformin (with or without an SGLT2 inhibitor). At week 32, the mean change in HbA1c from baseline was greater with the combination than with cagrilintide alone, and the mean change in body weight was greater with the combination than with either monotherapy. The safety profile of the combination was broadly consistent with the individual components, with gastrointestinal events the most frequently reported adverse events.

Researchers compared a weekly combination of cagrilintide plus semaglutide to each of the two compounds given alone, in adults with type 2 diabetes whose blood sugar wasn't well controlled on metformin. After 32 weeks, the combination produced larger reductions in average blood sugar (HbA1c) and larger body-weight reductions than either compound on its own. Side effects were mostly stomach-related, similar to either compound alone.